Method of preventing and treating acute brain pathologies

Abstract

Described are novel means in the treatment of cerebral neurological conditions such as ischemic insult of the brain. Furthermore, a kit for a non-radioactive protein serine/threonine phosphatase activity assay is provided, which is capable of detecting and distinguishing the activity of PP1, PP2A, and calcineurin (PP2B).

1 . An agent capable of maintaining, restoring or promoting phosphatase activity of protein phosphatase 1 (PP1) for the treatment, amelioration or prevention of an acute cerebral neurological condition. 
     
     
         2 . The agent of  claim 1 , wherein said neurological condition is due to an excitotoxic injury. 
     
     
         3 . The agent of  claim 1 , wherein said neurological condition is selected from the group consisting of stroke, head or spinal cord trauma, seizure, or neurodegenerative disorders. 
     
     
         4 . The agent of  claim 1 , wherein said neurological condition is acute ischemic insult. 
     
     
         5 . The agent of  claim 1 , wherein said agent is capable of inducing long-term depression (LTD). 
     
     
         6 . The agent of  claim 5 , which is low frequency stimulation (LFS). 
     
     
         7 . The agent of, wherein said agent is a PP1-activator/agonist. 
     
     
         8 . The agent of  claim 7 , wherein said agent is selected from the group consisting of ceramide, inhibitor-2, cdc2-cyclin B, and glycogen synthase kinase 3 (GSK3). 
     
     
         9 . A method of diagnosis of an acute neurological condition said method comprising:
 (a) assaying a sample from a subject for PP1 gene product or activity; and   (b) determining the level of PP1 gene product or activity,   wherein an altered level compared to a control indicates the presence of the condition.   
     
     
         10 . (canceled) 
     
     
         11 . A kit for the non-radioactive detection of the activity of PP1, PP2A, and calcineurin (PP2B), comprising:
 (a) an inhibitor that preferentially inhibits either PP1 alone or PP2A alone;   (b) a compound capable of interfering with protein kinase A activity and blocking phosphorylation-dependent endogenous phosphatase inhibitors;   (c) a compound capable of blocking calcineurin activity; and optionally   (d) a phosphatase substrate.   
     
     
         12 . The kit of  claim 11 , wherein said inhibitor of (a) is tautomycin and/or okadaic acid, said compound of (b) is caffeine, said compound of (c) is EDTA, and/or said substrate is RII phosphopeptide. 
     
     
         13 . The kit of  claim 11 , further comprising calmodulin. 
     
     
         14 . The kit of  claim 11 , further comprising TCA. 
     
     
         15 . The kit of  claim 11 , further comprising a PiBind desalting resin. 
     
     
         16 . The kit of  claim 11 , further comprising a means for colorimetric detection of inorganic phosphates. 
     
     
         17 . The kit of  claim 12 , further comprising calmodulin. 
     
     
         18 . The kit of  claim 12 , further comprising TCA. 
     
     
         19 . The kit of  claim 13 , further comprising TCA. 
     
     
         20 . The kit of  claim 12 , further comprising a PiBind desalting resin. 
     
     
         21 . The kit of  claim 13 , further comprising a PiBind desalting resin.